Sarepta - MIS51ON
A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of a High Dose of Eteplirsen, Preceded by an Open-label Dose Escalation, in Patients With Deletion Mutations Amenable to Exon 51 Skipping
This phase 3 study is designed to evaluate the safety and tolerability of two doses of eteplirsen. Part One will be investigating two doses with Part 2 comparing the most effective dose from Part 1 with a 30mg/kg dose of eteplirsen. The UK sites have not yet been finalised, we will provide an update once we have these details.
Study Number: NCT03992430
Description by Sarepta Therapeutics
This study will be comprised of 2 parts: Part 1 will be conducted to evaluate the safety and tolerability of two doses (high dose level 1 and high dose level 2) of eteplirsen in approximately 8 patients; Part 2 will be conducted for the selection of a high dose (high dose level 1 vs high dose level 2) (dose finding phase), and its comparison with the 30 mg/kg dose of eteplirsen (dose comparison phase), in approximately 144 DMD patients with genetically confirmed deletion mutations amenable to treatment by skipping exon 51.
Primary Outcome Measures
- Part 1 and Part 2 (Dose Finding): Incidences of Adverse Events (AEs) [ Time Frame: Baseline up to Week 148 ]
- Part 2 (Dose Finding): Dystrophin Expression in Biopsied Muscle Tissue [ Time Frame: Up to Week 48 ]
- Part 2 (Dose Finding): Pharmacokinetic (PK) Plasma Concentration of Eteplirsen [ Time Frame: Multiple timepoints up to Week 48 ]
- Part 2 (Dose Finding): Tissue Concentration of Eteplirsen From Biopsied Muscle Tissue [ Time Frame: Up to Week 48 ]
- Part 2 (Dose Comparison): Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score [ Time Frame: Baseline, Week 144 ]
Secondary Outcome Measures
- Part 2 (Dose Comparison): Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) [ Time Frame: Baseline up to Week 144 ]
- Part 2 (Dose Comparison): Change From Baseline in Time to Complete Walk/run, Stairs and Time to Rise [ Time Frame: Baseline up to Week 144 ]
- Part 2 (Dose Comparison): Annual Rate in Decline of Forced Vital Capacity Percent Predicted (FVC%p) [ Time Frame: Up to Week 144 ]
- Part 2 (Dose Comparison): Time to Loss of Ambulation (LOA) [ Time Frame: Baseline up to Week 144 ]
- Part 2 (Dose Comparison): Change From Baseline in Skeletal Muscle Dystrophin Expression [ Time Frame: Baseline and Week 48 ]
- Part 2 (Dose Comparison): Incidence of Adverse Events (AEs) [ Time Frame: Baseline up to Week 144 ]
Can I take part?
- Be a male with an established clinical diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping.
- Have achieved a mean 6-minute walk test (6MWT) distance of greater than equal to (>=) 300 and less than equal to (<=) 450 meters.
- Have intact right and left biceps muscles or an alternative upper arm muscle group.
- Have been on a stable dose or dose equivalent of oral corticosteroids for at least 24 weeks prior to randomization.
- Have stable pulmonary function (forced vital capacity >= 50 percent (%) of predicted and no requirement for nocturnal ventilation).
- Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to randomization.
- Current or previous treatment with gene therapy or any other experimental pharmacologic treatment for DMD; some exceptions apply.
- Previous treatment with drisapersen, ezutromid, or domagrozumab in the last 24 weeks prior to study enrollment.
- Major surgery within 3 months prior to randomization.
- Presence of any other significant neuromuscular or genetic disease other than DMD.
- Presence of other clinically significant illness.
- Has evidence of cardiomyopathy, as defined by left ventricular ejection fraction less than (<) 50% on the screening Echocardiogram or QTcF >= 450 millisecond based on the screening ECGs.
Other inclusion/exclusion criteria apply.